White Paper: The Value Of Robust Exploratory Toxicology Testing Prior To Pivotal GLP Studies
Over the years, the pharmaceutical industry has made steady progress in improving the safety of drugs in development. Consequently, in 2015, only 14 percent of Phase III studies failed due to safety (compared to 55 percent for efficacy), down from 21 percent in 2013. In other words, “efforts to remove unsafe agents earlier in the development cycle are paying off.” Much of this success in small molecules relates to careful and methodical work done well before the Investigational New Drug (IND) application.
Journal: Simultaneous Quantification Of Total Antibody And Antibody-Conjugated Drug For XMT-1522 In Human Plasma Using Immunocapture-Liquid Chromatography/Mass Spectrometry
XMT-1522, an antibody-drug conjugate (ADC) currently in Phase I clinical development, represents the first Dolaflexin®-based, cleavable ADC with a high drug-antibody ratio (DAR). In this work, a novel immunocapture LC–MS/MS method was successfully developed for the simultaneous quantification of both total antibody and cleavable antibody-conjugated drug auristatin F-hydroxypropylamide (AF-HPA) in human plasma. This method utilized microwave-assisted enzymatic digestion for the total antibody and chemical release of the drug from ADC on a 96-well based immunocapture sample preparation platform. The total antibody and the conjugated drug AF-HPA were separated and subsequently quantified concurrently by LC–MS/MS. The linear range of the standard curve for total antibody was from 50 to 5000 ng/mL and for AF-HPA was from 3.3 to 330 ng/mL. The linearities showed R2 ≥ 0.993 for total antibody and R2 ≥ 0.996 for AF-HPA, respectively. The intra- and inter-day precision and accuracy were well within 15%. The validated method, with the characteristics of high efficiency, great selectivity, free of carryover, short LC–MS/MS time (˜3.5 min) and low sample volume (20 μl), was successfully applied for analyzing Phase 1 cancer patient samples.
Fact Sheet: Bioanalytical Large Molecule
Gain access to comprehensive biologics services in support of advanced development programs with Frontage’s bioanalytical laboratory. We have the capabilities to analyze virtually any peptide, protein or antibody, and have built a reputation for solving technical challenges related to assay development and validation.
Assay List: Biomarker Assay List – April 2019
Frontage’s Bioanalytical Team is highly experienced in developing, qualifying and validating Biomarker assays. We can apply traditional and newer ELISA platforms as well as ultra-sensitive detection capabilities (Quanterix Simoa) for quantitation in the femtogram/mL range including single and multiplex analysis in various disease categories. Check out our updated list of Biomarker Assays.
Corporate Deck: Frontage Laboratories Overview Deck 08.2019
We are a CRO providing integrated, scientifically-driven research, analytical and development services throughout the drug discovery and development process to enable biopharmaceutical companies to achieve their drug development goals. We have enabled many innovator, generic and consumer health companies of all sizes to file IND, NDA, ANDA, BLA and 505(b)(2) submissions in global markets allowing for successful development of important therapies and products for patients. We are committed to providing rigorous scientific expertise to ensure the highest quality and compliance. We have successfully assisted clients to advance hundreds of molecules through development to commercial launch in global markets.
Fact Sheet: CMC GMP Analytical Testing
Biologics or biopharmaceuticals are inherently more complex than small-molecule drugs. You need the right team to help you. Frontage has expertise and state of the art instrumentation necessary for the analytical method development, validation and transfer for complex biopharmaceutical compounds. Using bottom up, middle up/down, and top down approaches, we offer analytical support for characterization of primary, secondary and tertiary structures, post translational modifications such as glycosylation, disulfide linkage, antibody drug conjugation, or PEGylation.
Poster: Pre-Existing Antibodies within Immunogenicity Testing
Monoclonal antibodies and next generation molecules such as antibody-drug conjugates (ADC) are being developed and moved into early phase clinical testing. These new molecules bring challenges for measuring immunogenicity within human serum samples.
• Therapeutic monoclonal antibodies could have structural regions which could contain ADA binding domains [Figure 1].
• ADC molecule has a mAb joined to a small drug by a linker region [Figure 2]. This may lead to a highly potent drug which is also a selective binder of a specific tumor antigen; however, the structure may also present a neoepitope to the immune system.
• Development of anti-drug antibody (ADA) assays to both mAb’s and ADC’s very commonly has demonstrated the presence of pre-existing antibodies (PEXA) in a small percentage of drug naïve normal human serum samples. It is currently unclear as to the evolutionary mechanism that has allowed PEXA to develop. Their presence may serve as a regulatory mechanism to suppress the immune system under certain conditions.
• Regardless of how pre-existing antibodies may have developed, measuring an anti-drug antibody (ADA) response in serum samples may present additional challenges with these pre-existing molecules present. Here, we outline a strategy to determine where on the molecule the ADA reactivity is directed against.